Time travel with viruses

Viral infections leave trace information in our tissues. Researchers can read it like a history book extending from mediaeval smallpox epidemics to ancient Egypt.

Virologist Mari Toppinen began her journey through history at a lecture on identifying war dead, focusing on corpses left on the Russian side of the border after the war between Finland and the Soviet Union. The dead have been transported to Finland for identification, beginning in 1992.

“I was listening to professor of forensic medicine, Antti Sajantila, and I started wondering if the bones on the former battlefield could have signs of parvovirus, which was one of the research topics of our group,” Toppinen says. “During the infection, the parvovirus multiplies specifically in the bone marrow.”

The parvovirus causes a common, typically harmless disease known as fifth disease, which is characterised by an intense red rash. Scientists at the Department of Virology in the Academic Medical Center Helsinki place a special significance on it: It was while studying the very parvovirus that they found what a fascinating compendium of information viruses can leave in the tissues of their hosts during their visit.

Toppinen and her colleagues joined forces with forensic scientists, and found parvovirus DNA in the bones. “We analysed 106 of the war dead. Approximately every other individual had traces of the virus, despite the bones being exposed to UV radiation and the acidic earth.”

SURPRISE FROM THE CAUCASUS

One of the unanswered questions surrounding the parvovirus is why it abruptly changed after World War II. While the symptoms remained largely the same, something changed beneath the surface: the type 2 virus which had actively circulated in Finland for ages disappeared before the 1970s and was replaced by the type 1 virus.

As expected, most of the findings in the war dead were of the old type 2 virus, but the researchers also found a surprise. Two of the dead had experienced an infection caused by the type 3 virus, which is extremely rare in the Nordic countries.

“It turned out that these two had roots in the Caucasus. This means that even though we assumed they were Finnish, they may have been soldiers from the Red Army,” Toppinen explains.

This case of the men who made their way from one of the borders between Asia and Europe to Karelia proved that viral traces could help researchers uncover the life histories of individuals. However, the riddle of the disappearing type 2 parvovirus remains unsolved.

MULTITUDES OF MUMMIES

Mari Toppinen is working on her doctoral dissertation in Professor Klaus Hedman’s laboratory. The internationally acclaimed professor of clinical virology is similarly preoccupied by the past. “We can suddenly ask the same questions of the past that we have been asking about the present. A whole new world has opened up right behind our back window.”

The primary reason for this new access to the past is new technology, including gene duplication methods as well as new information technology, databases and increased processing power.

Hedman and his colleagues are already thinking beyond World War II, to the time of the European colonisation of America and Europe’s smallpox epidemics, even to ancient Egypt. They are also interested in Neanderthals.

“We were surprised when we discovered how many mummies there are. We originally thought that we would primarily be analysing bones if we were interested in ancient tissue samples.”

THE MOTHER OF ALL SMALLPOX

Last year, Hedman and his partners published an article in the journal Current Biology which changed the way we think about the origins of smallpox. Smallpox has been one of the deadliest diseases in human history, and it is assumed to have originated millennia ago, in ancient Egypt, India and China.

The new research was helped along by a child, a Lithuanian victim of smallpox. Together with researchers from McMaster University in Canada, Hedman’s team studied the background of the child mummy stored in a crypt in Vilnius. Radio carbon dating revealed its age to be approximately 350 years.

Analysing the fragmented viral traces was quite the feat of molecular technology, but they got results. “From this mummy, we managed to reconstruct the mother of all smallpox strains – the oldest smallpox virus ever found.”

Professor Hedman gives primary credit for this achievement to postdoctoral researcher Maria Perdomo, who had the main responsibility for the smallpox analysis. The researchers found that the ancestral form of the smallpox virus was born less than 500 years ago, around 1580.

This would mean that stories of smallpox disasters in the courts of the pharaohs are decidedly untrue, and that Pharaoh Ramesses V probably died of some other disease. “Perhaps the Egyptians suffered from another similar illness,” says Hedman.

A NEW GOLDEN AGE

The parvovirus is a relatively easy research subject, as it leaves traces everywhere, including the skin, joints and liver. For many other viruses, traces must be sought from a very specific tissue, on a case-by-case basis.

Professor of genetic and forensic medicine Antti Sajantila has become an important partner also in the study of contemporary illnesses. Hedman’s group intends to go through pathologists’ autopsy patients, systematically searching for traces of various viruses. “How wrong were the people who predicted that the golden age of virology would be over as soon as illnesses such as rubella and polio are eradicated!”

LIKE A DINOSAUR

Klaus Hedman is fascinated by the geographical movements of diseases over the past centuries. “It would be amazing to find out what kinds of diseases circulated in America before the conquistadors came along!” Did the Europeans bring illnesses with them, or did they bring New World diseases to Europe? And what about even further back in history?

Hedman describes a study conducted by Ville Pimenoff, who relocated to Spain from Finland. Pimenoff’s modelling research revealed that the papillomavirus type HPV16, which is responsible for many contemporary cases of cervical cancer, came to modern humans as a sexually transmitted disease from the Neanderthals. “It’s possible that the virus had little effect on Neanderthals,” says Hedman.

Hedman believes that archaeovirology, the study of ancient history by studying the evolution of viruses, is as exciting as hunting for exotic fossils. “Zoologists look to the past and find dinosaurs. What might we find? Perhaps something that no longer exists, something we can’t even imagine.”

Could viruses be beneficial to people?

“Every virologist dreams of being able to announce that viruses are as important for humans as the bacteria in our intestines, for example. But nothing points to that yet,” professor Klaus Hedman says.

However, the global threat of superbacteria is raising interest in viruses. If antibiotics are ineffective in our battle against these bacteria, we will have to find other methods. One factor is the viral load inside humans – and particularly the viruses housed inside the bacteria in our bodies, i.e., bacteriophages.

“Phage therapy is a partial solution as resistance to antibiotics becomes more common. Bacteriophages keep their hosts in check,” says Hedman.

Naked viruses

Klaus Hedman’s laboratory specialises in small, non-enveloped — or “naked” — DNA viruses. Non-enveloped viruses only have the nucleoprotein capsid, with no membrane envelope derived from the host cell of the virus.

DNA viruses are a group of viruses whose genetic material is in the form of DNA, as is common in organisms generally. In other viruses, their genetic information is encoded in RNA.

“Medicine recognises many mystery viruses whose effects are unknown, and also diseases with unknown causes. Together with Docent Maria Söderlund-Venermo, we are trying to make this ‘supply’ meet the ‘demand’,” states the professor.

During the past decade or so, researchers have discovered one naked DNA virus after another in humans, approximately twenty in total, and responsible for a multitude of ailments ranging from respiratory infections to cancer.